Acute myocarditis with thrombus near left ventricular outflow tract

A young woman presented with fulminant heart failure. Transthoracic echocardiography revealed severe left ventricular dysfunction with a mass adjacent to the basal anterior wall, near the left ventricular outflow tract (LVOT). The cause of the acute heart failure and mass was unclear. Transesophageal echocardiography, with contrast, and cardiac magnetic resonance imaging findings were consistent with thrombus near the LVOT. Cardiac biopsy suggested giant cell myocarditis. The patient was treated with anticoagulation, steroids, and heart failure medications with resolution of the thrombus. This case was remarkable for the location of thrombus at the base of the ventricle.     

Application of LC/MS to determine specific activity variation in a series of sulfonamide tracers from the [35S]methane sulfonate reagent

The specific activities for a series of S‐35 tracers were found to vary from the decay‐corrected specific activity of the labeled reagent. If not known before the stock solution preparation and binding assay, this variation would have resulted in performing the assay at approximately two to three times over the targeted concentration, thereby leading to considerable error in the calculated binding and related conclusions. Copyright © 2012 John Wiley & Sons, Ltd.     

Adherence to nebulised therapies in adolescents with cystic fibrosis is best on week-days during school term-time

ObjectivesTreatment regimen for families of children with cystic fibrosis (CF) is considerable, particularly when nebulised therapies for chronic Pseudomonas aeruginosa airway infection are prescribed. Adherence to these regimens is variable, particularly in adolescence. Previously, we reported children to be more adherent in evenings compared to mornings, suggesting an association with time-pressure. The aim of this study was to determine whether adherence would be better in adolescent patients at weekends and during school holidays when time-pressures may be less.Study design24 patients (14 male, median [range] age 13.9 [11.1–16.8] years) were enrolled from two regional paediatric CF centres in the United Kingdom. Data for a full scholastic year, were downloaded openly from a breath-activated data logging nebuliser (I-neb?). Adherence (% of doses taken ÷ expected number) was calculated during term-times, holidays, weekends and weekdays, for each patient.ResultsLarge variations in adherence were seen between patients. However, adherence during term-time was significantly better than holidays (p < 0.001). Weekday adherence was better than weekend adherence in term-time but not holidays. Interestingly, patients prescribed three daily treatments took on average 1.4 treatments/day, a similar number to those prescribed two daily treatments.ConclusionOverall adherence to inhaled therapies was reasonable, but significantly reduced during holiday periods. This suggests a need for families to have not only time, but also structure in their daily routine to maintain optimal adherence to long-term therapies. It is important for CF teams to appreciate these factors when supporting families.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

B cells mediate chronic allograft rejection independently of antibody production

Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.